Pharmaceutical compositions

ABSTRACT

A composition of an antitussive, a decongestant, or an antihistamine to treat upper respiratory and oral pharyngeal congestion and related symptoms in a patient.

CROSS-REFERENCES TO RELATED APPLICATIONS

This Application is a continuation of application Ser. No. 14/733,731,filed Jun. 8, 2015, which is a continuation of application Ser. No.13/703,584, filed Dec. 11, 2012, which is a US national stageapplication of PCT/US2011/040231 under 35 U.S.C. §371 filed Jun. 13,2011, which claims priority from U.S. Provisional Patent Application No.61/354,053 filed Jun. 11, 2010, U.S. Provisional Patent Application No.61/354,057 filed Jun. 11, 2010, and U.S. 61/354,061 filed Jun. 11, 2010,all of which are hereby incorporated by reference as if fully set forthherein.

FIELD OF THE INVENTION

The present invention relates to the treatment and relief of varioussymptoms of upper respiratory and oral pharyngeal congestion, and inparticular, to a combination medication for treatment and reliefthereof.

BACKGROUND OF THE INVENTION

People around the world frequently suffer from upper respiratory tractand oral pharyngeal congestion. This congestion may be caused byallergies, infections in the respiratory tract and/or oral andpharyngeal cavities, changes in weather conditions, as well as from theoverall health and genetic disposition of the person. This congestion isgenerally diagnosed from partially or fully blocked air passagesincluding airways in the lungs, mouth, nose, and throat. Other symptomsrelated to the cause typically accompany the congestion. Cough, ticklesin the throat, cold symptoms such as fever, flu, sinus infections, andthroat or gland pain are some of the more common symptoms found withupper respiratory and oral pharyngeal congestion.

Congestion of the upper respiratory tract and oral pharyngeal cavity andrelated symptoms generally have undesirable effects for the afflictedperson. For example, the congestion may affect performance in theworkplace, school, and at home up to and including loss of work and lossof school attendance. Further, congestion may reduce the ability toperform routine activities, such as housework, driving, running errands,and may even totally incapacitate the person. Severe and intolerablecongestion often requires visits to the hospital and treatment. Inaddition, viral or bacterial infections of the sinus passage or otherairway may be passed to healthy persons through symptoms of thecongestion. For example, a cough or sneeze may convey a bacterium orvirus to another person. Thus, upper respiratory tract and oralpharyngeal congestion and its symptoms need to be treated.

Generally, there are two typical approaches to treating symptoms of thecongestion. One approach involves initially treating the underlyingcause of the symptom. For example, a bacterial infection is generallytreated by administering an antibiotic to kill the bacteria causing theinfection. The second approach involves treating the symptomsthemselves, typically in addition to treating the underlying cause, byindependently administering one or more medications for relief ofspecific symptoms. For example, an antitussive agent, commonly referredto as a cough suppressant, has been typically administered for thetreatment or relief of cough. An opioid medication, such as codeine andhydrocodone bitartrate, has generally been administered to relieve painconsistent with the congestion while suppressing a cough. Alsodecongestants, such as phenylephrine and pseudoephedrine, have beenadministered to both children and adults in flavored formulations forreducing mucosal swelling and draining the mucus build-up to clearcongestion in the air passages. Symptoms due to allergies or allergensare often treated with an antihistamine. Antihistamines, often referredto as histamine-class receptor blockers, are compounds that mayantagonistically block the histamine receptor from binding histaminethereby preventing the symptoms of an allergy.

There are many different treatment medications utilizing a combinationof agents in therapeutic doses for treating multiple symptoms of upperrespiratory tract and oral pharyngeal congestion. As one example, asingle medication may include an expectorant, in combination with anantitussive agent, for removing phlegm or mucus that may haveaccumulated in the lungs and other air passages in addition tosuppressing a cough. The expectorant is helpful in preventing theprogression of a mild case of bronchitis to a more severe case ofpneumonia.

Combination therapy provides many benefits. For example, it allowspatients suffering from congestion and related symptoms to take only asingle dosage medication, as opposed to multiple medications, for relieftherefrom. Further, it enhances compliance in accordance with a regimenby eliminating the need for the patient to take different medications.To this end, combination therapy provides convenience, ensurescompliance, and saves cost.

Combined treatment medications may be formulated as syrups, pills,tablets, and capsules. Formulations may include flavoring agents to maskundesirable flavors or tastes from desired medicinal agents andcolorants to render the medication more attractive and appealing to theeye. For example, many formulations have a raspberry, cherry, orange, orgrape flavor well liked by both children and adults. Moreover, theseflavors are easily identified by their color. In combinationformulations, the individual ingredients are included in amounts provento be effective to treat targeted symptoms. Effective amounts havevaried depending on the particular formulation, type and degree of thesymptoms, and desired user or consumer. For example, a child's dose ofan elixir or syrup for the relief of cough and pain related tocongestion may have the antitussive and analgesic in reduced quantitiesbased on size, weight, and age of the child targeted, comparable to acomposition or formulation for an adult which may have double the dosageof the antitussive and analgesic.

Accordingly, it is desirable to have an administrable composition toreduce symptoms of upper respiratory tract and oral pharyngealcongestion. It is further desirable that the composition be effective inreducing cough, congestion, histamine-stimulated allergy symptoms andrelated pain. Still further, it is desirable for the composition tocontain dosages suitable for administration to a child as well as anadult. In addition, it is desirable to have the composition in aconvenient and pharmaceutically acceptable dosage form.

SUMMARY OF THE INVENTION

The present invention provides compositions and methods for treatingupper respiratory and oral pharyngeal congestion and related symptoms ina person suffering therefrom. To this end, and in accordance with theprinciples of the present invention, there is provided a composition ofa decongestant, and an antihistamine. Optionally, a composition mayinclude an antitussive, an expectorant and an analgesic. The combinationof an antitussive, a decongestant, and an antihistamine in a singlecomposition provides relief of cough, congestion in the air passageways,and common allergy-type symptoms resulting from exposure to variousallergens, in a convenient and effective dosage formulation.

The composition is formulated in pharmaceutically acceptable forms suchas liquids, pills, capsules, tablets, and the like. Suitable capsuleforms include, without limitation, liquid gelatin capsules andenteric-coated capsules. The tablet form may be chewable, may melt ordisintegrate in the mouth, or may be enteric-coated to providedelayed-release and sustained-release characteristics for thecomposition. In one embodiment, the composition is formulated into aliquid. The composition may further include other components, such asconventional excipients including binders, colorants, fragrances, andthe like, to render the composition more attractive and suitable foruse.

By virtue of the foregoing, there is thus provided compositions andmethods for treating upper respiratory and oral pharyngeal congestionand related symptoms in effective formulations. These and other benefitsand advantages of the present invention shall be made apparent from theaccompanying detailed description thereof.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The present invention provides compositions and methods for treatingupper respiratory and oral pharyngeal congestion and related symptoms ina patient in need thereof. The term “upper respiratory and oralpharyngeal congestion” as used herein includes congestion in the oral,pharyngeal, nasal, and bronchial passages of the upper respiratorytract. It also is intended to include other symptoms, such as cough andpain related to allergies, infections, colds, coughs, flu, viral andbacterial infections, and other common causes for the congestion. Thus,multiple symptoms including congestion may be treated with thecompositions of the present invention. Treatment includes a reduction inseverity or duration, delay in onset, and/or general relief of one ormore of these symptoms. The term is intended to refer to congestion asdescribed herein, as well as to a wide range of symptoms related to thecongestion or its cause and treatable with the present compositions. Forexample, symptoms related to a common cold or flu such as cough, fever,and the like, and allergy symptoms such as hives, breakouts, swelling,and runny nose due to external stimulants are treated with the presentcompositions. In addition, symptoms, such as congestion, cough, pain anddiscomfort associated with the congestion, resulting from a bacterial orviral infection, particularly an infection in the respiratory tract, arealso treated with the present compositions. The term “congestion”, asuse herein, is intended to refer to the narrowing of an airway includingthe oral, pharyngeal, nasal and bronchial passages due to fluid or asolid substance, such as mucus or phlegm. Narrowing of the airway isoften due to swelling or inflammation of the mucous membrane lining thepassage to result in a partially or fully blocked passage. Severe casesof congestion often cause difficulties in breathing. Besides allergicreactions, infections, and common cold and flu, the symptoms describedherein may also be due to poor health or a predisposition for thesymptom through genetic make-up. The terms “treating” and “alleviating”,as used herein with respect to upper respiratory and oral pharyngealcongestion and related symptoms, include any reduction in severity orduration, of any degree, of the congestion and/or one or more of therelated symptoms. The terms also include any delays in onset of and anygeneral relief from the congestion and/or one or more of the relatedsymptoms. Thus, the present invention encompasses palliativecompositions and methods.

To this end, and in accordance with the principles of the presentinvention, the compositions include an antitussive, a decongestant, andan antihistamine. Inclusion of an antihistamine, in combination with anantitussive and a decongestant provides relief of histamine-stimulatedallergy symptoms in addition to relieving other symptoms, such as cough,congestion, swelling, and pain. These added benefits provide increasedefficacy and translate into convenience and cost savings for thepatient.

The present invention provides pharmaceutical compositions containing anantihistamine along with a decongestant and optionally an analgesic oran antitussive. The compositions of the invention may be administered ineffective dosages for treating nasal congestion symptoms. To this end,the pharmaceutical compositions include at least one antihistamine andat least one stimulant. The most potent antihistamines are generallysedating in nature and the sedation is reduced or alleviated with thestimulant. The compositions are useful for treating allergic reactionsand other histamine-mediated symptoms, as well as for providing otherphysiological effects including, for example, anticholinergic effects,analgesic effects, analgesic adjuvant effects, soporific effects,anti-secretory effects, and combination effects thereof. By combining apotent, effective antihistamine with an effective, anti-sedatingstimulant, the compositions of the present invention may be administeredmore safely than prior art antihistamine-containing medications utilizedfor the same purpose. The present invention also provides methods of usefor the pharmaceutical compositions.

Antihistamines suitable for the compositions include, withoutlimitation, diphenhydramine, cyproheptadine hydrochloride,brompheneramine, hydroxyzine, chloropheniramine, pyrilamine maleate,pyrilamine tannate, acepromazine, aceprometazine, alimemazine,alimemazine tartrate, amoxydramine camsilate, antazoline chlorhydrate,antazoline mesilate, antazoline phosphate, astemizole, azatadinedimaleate, azelastine hydrochloride, bamipine hydrochloride, benactyzinehydrochloride, bretylium tosilate, bromazine hydrochloride,brompheniramine maleate, buclizine dihydrochloride, bufexamac,carbinoxamine maleate acid, cetiedil citrate, cetirizinedihydrochloride, chlorcyclizine hydrochloride, chlorphenamine maleate,chlorphenoxamine hydrochloride, chlorprothixene hydrochloride,cinnarizine, clemastine fumarate, clemizole hexachlorophenate, clemizolepenicilline, clemizole undecylenate, clocinizine dihydrochloride,clofedanol, clofenetamine hydrochloride, cyclizine hydrochloride,dexchlorpheniramine maleate, di (acefylline) diphenhydramine,difencloxazine, dimelazine hydrochloride, dimenhydrinate, dimethoxanatehydrochloride, cimetotiazine mesilate, diphenhydramine hydrochloride,diphenhydramine mesilate, diphenylpyraline hydrochloride, diproqualonecamsilate, dixyrazine, doxylamine succinate, eprozinol dihydrochloride,etodroxizine dimaleate, etybenzatropine bromhydrate, etybenzatropinehydrochloride, etymemazine hydrochloride, fenethazine hydrochloride,fenoxazoline hydrochloride, fenpentadiol, flunarizine hydrochloride,flupentixol decanoate, flupentixol dihydrochloride, histapyrrodinehydrochloride, hydroxyzine dihydrochloride, hydroxyzine embonate,indoramine hydrochloride, isothipendyl hydrochloride, ketotifenefumarate, levocabastine hydrochloride, levomepromazine, levomepromazinehydrochloride, levomepromazine embonate, levomepromazine maleate,loratadine, maprotiline hydrochloride, maprotiline mesilate, maprotilineresinate, meclozine hydrochloride, mecysteine hydrochloride,medifoxamine fumarate, mefenidramium metilsulfate, mepyramine maleate,mequitazine, methaqualone, methdilazine hydrochloride, metixenehydrochloride, mizolastine, moxisylyte hydrochloride, niaprazine,orphenadrine hydrochloride, oxaflumazine disuccinate, oxatomide,oxolamine benzilate, oxolamine citrate, oxomemazine, oxomemazinehydrochloride, parathiazine teoclate, perimetazine, pheniramine maleate,phenoxybenzamine hydrochloride, phenyltoloxamine, phenyltoloxaminecitrate, pimethixene, pipotiazine, pipretecol dihydrochloride,pizotifene malate, prednazoline, profenamine hydrochloride,promethazine, promethazine hydrochloride, promethazine embonate,promethazine polyvinylbenzene-metacrylate, propiomazine, terfenadine,thenalidine tartrate, thenyldiamine hydrochloride, thiazinamiummetilsulfate, thonzylamine hydrochloride, tripelennamine hydrochloride,triprolidine hydrochloride, and tymazoline hydrochloride, andcombinations thereof.

The antihistamine is included in an amount, per dosage of thecomposition, sufficient to alleviate one or more histamine-mediatedresponses in a patient. Effective doses of the antihistamine willgenerally vary depending upon the antihistamine (s) administered.

The present composition also includes an antitussive. The term“antitussive”, as used herein, is intended to include any agent oractive ingredient effective for cough suppression such as chlophedianolhydrochloride. These also include, but are not limited to, common opioidanalgesics such as hydrocodone, codeine, morphine, morphine-relatedcompounds including diacetylmorphine, oxymorphone, hydromorphone,dextromethorphan, levorphanol, oxycodone, nalmefene, methadone,meperidine, pentazocine, buprenorphine, nalbuphine, butorphanol,sufentanyl, alfentanyl and propoxyphene, and opioid antagonists notstructurally-related to morphine, such as nalorphine, naloxone,naltrexone and fentanyl. In one embodiment, the antitussive agent ishydrocodone or a pharmaceutically acceptable salt form thereof, such ashydrocodone bitartrate.

The present composition also includes a decongestant. The term“decongestant” as used herein, is intended to refer to any agent oringredient, active for reducing or eliminating congestion of the airpassages by widening the airway, and/or by stimulating the release ofphlegm and mucus from these passages. Air passages may be widened byreducing the swelling of the mucous membranes in the passage. Generally,sympathomimetic drugs have decongestant properties. Examples of suitabledecongestants include, without limitation, phenylethylamine,epinephrine, norepinephrine, dopamine, dobutamine, colterol,ethylnorepinephrine, isoproterenol, isoetharine, metaproterenol,terbutaline, metaraminol, phenylephrine, tyraine, hydroxyamphetamine,ritodrine, prenalterol, methoxyamine, albuterol, amphetamine,methamphetamine, benzphetamine, ephedrine, phenylpropanolamine,mephentermine, phentermine, fenfluramine, propylhexedrine,diethylpropion, phenmetrazine, phendimetrazine, oxymetazoline,xylometazoline, and pseudoephedrine.

It should be understood that an effective amount of the antitussive andthe decongestant generally vary with the particular antitussive anddecongestant chosen. In addition, an effective amount depends upon manyother factors, such as known differences in pharmacokinetic parameters(absorption, distribution and clearance) regardless of the cause. Forexample, in a patient with a renal dysfunction or disorder, theeffective dose of the antihistamine, the antitussive, and thedecongestant is generally half of an effective dose for a patientwithout renal dysfunction.

While the present composition includes an antitussive, a decongestant,and an antihistamine, the present composition is not so limited and mayinclude other components. These components include conventionalexcipients, useful and/or desirable to render the composition suitableor attractive for consumption and use. Excipients providing physical andaesthetic properties for formulation or delivery of the composition aredesirable. For example, with respect to physical properties, ingredientsimparting desirable and acceptable hardness, disintegration properties,dissolution rate for release of therapeutic components, stability, andsize to effectively deliver the composition may be included.Disintegrants may be included for the purposes of facilitating thebreakup of a tablet after the tablet is administered to the patient.Examples of disintegrants include, but are not limited to, modified orunmodified starches such as cornstarch, potato starch, wheat starch, orsodium cross-carmellos. With respect to aesthetics, it may be desirablefor the composition to contain additives that appeal to the human sensessuch as colorants, fragrances, texture modifiers, and/or flavorants.Additionally, many flavoring agents such as, for example, fruit flavors,or sweeteners, such as sodium saccharin, confectionery sugar, sucrose,xylitol, or combinations thereof, may be included. Additionally,suitable colorants including, for example, red beet powder, ferricoxide, FD&C dyes, or combinations thereof, may be included in thepresent compositions. Desirable excipients may also include bufferingagents, surfactants, electrolytes, and thixotropic agents. It should beunderstood that these other components should not affect the action ormechanism of action of the antitussive, decongestant, and/or theantihistamine in the composition.

Excipients or formulations affecting the release properties, mechanisms,and/or rates of the antitussive, the decongestant, and theantihistamine, from the composition upon oral ingestion may be provided.For example, the composition may be formulated such that the release ofthe antitussive, the decongestant, and/or the antihistamine or otheractive ingredients from the composition is delayed for a period of timeor to survive a particular environment.

Advantageously, the composition may be formulated so as to prevent therelease of the antitussive, the decongestant, and/or the antihistaminein the stomach where they may likely be acidified, salted out andexcreted from the body rather than absorbed into the circulation. Forexample, the composition may be coated with a coating to improveabsorption and render the composition more bioavailable than it wouldotherwise be without the coating. Enteric coatings or encapsulation-typecoatings as known to one skilled in the art are suitable for thispurpose. In one embodiment, a table or a capsule form of the compositionis enterically coated so as to provide delayed-release andsustained-release properties to the composition. Sustaining the releaseof individual active ingredients to the body over a period of timeprolongs the effective time period of relief from the congestion andrelated symptoms, provided, however, the amount of the ingredient in theblood stream is within the effective therapeutic window for thatparticular ingredient. Further, preservatives may be provided to preventdegradation of components in the composition or degradation of thecomposition as a whole, thereby improving the stability and prolongingthe shelf life of the composition.

The composition of the present invention may be formulated in a singleform. In one embodiment, the form is convenient to swallow, and has agenerally accepted appearance and taste to promote consumption andcompliance with a dosing regimen. In accordance with one aspect of thepresent invention, the composition is formulated into a dosage form thatmay be an ingestible liquid, a pill, a tablet, a capsule, a suppository,etc. In accordance with another aspect of the invention, the compositionmay be formulated into a parenterally administrable form. It should beunderstood by one skilled in the art that certain active agents, such ashydrocodone, are typically not parenterally administered, such as byintra-venous administration. However, other opioids such as codeine,morphine, methadone, and fentanyl may be administered with antihistaminein a non-orally administrated formulation. In accordance with a furtheraspect of the invention, the present composition may include activeingredients suitable for sub-lingual administration. In accordance withyet another aspect of the invention, the present composition may beadministered via mucous membranes of the buccal, nasal, rectal cavities,etc. The desired formulation may be prepared by a process known in theart of pharmaceutical manufacture. For example, liquid formulations maybe prepared in the form of a syrup or a suspension. In one embodiment,the composition is formulated into an elixir or a syrup having adesirable flavor for easy, trouble-free administration to a child.

Solid formulations, such as capsules may be prepared by first blendingthe antitussive, the decongestant, and the antihistamine with otherdesirable additives and then filling capsular materials with the blendedmixture using conventional filling equipment. In one embodiment, thecapsular material is a gelatin. The capsule formed may be a liquidgelatin capsule. Further, where desired, the capsule may be coated foradded benefits. In general, tablets may be formed by first blending thecomponents and then either directly compressing the blended components,or granulating the components followed by compressing them into a tabletform. Additional ingredients may be included during compression wheredesired. For example, the granular mixture may contain one or morelubricants to inhibit sticking during compression. Examples of suitablelubricants include, but are not limited to, stearic acid, palmetic acid,stearates, talc, and oils.

The compositions of the invention may also be formulated as a powder orsprinkles.

To effectively suppress cough, relieve pain, and reduce mucus membraneswelling for reducing congestion and other blockage of air passages, thecomposition of the present invention includes the antitussive, thedecongestant, and the antihistamine in amounts suitable for treatingchildren and adults alike.

In yet another embodiment of the present invention, there is providedmethods of alleviating symptoms of upper respiratory and oral pharyngealcongestion by orally administering to a patient in need thereof a singledose of a composition or formulation including an antitussive, adecongestant, and an antihistamine. The patient in need may be a childor an adult suffering from the congestion. Administration of thecomposition will depend upon the form of the composition. For example, aliquid formulation may be administered to a child in amounts smallerthan that administered to an adult. Administration will also depend uponvarious other factors related to the patient. For example, age, health,weight, prior medical history, extent and degree of symptoms, andoverall medical diagnosis will generally influence the amountsadministered. The composition is generally administered for alleviatingcough, pain, cold and allergy symptoms and also provides a sedativeeffect, an analgesic adjuvant effect, an anticholinergic affect, and amild analgesic effect.

Formulations of the invention may contain any or all of the following inany combination: Purified Water; Any combination of permitted API'sadded as powders or as solutions, emulsions, suspensions: ChlophedianolHydrochloride, Pseudoephedrine Hydrochloride, Phenylephrine, or anyapproved oral nasal decongestant; Dexchlorpheniramine Maleate,Dexbrompheniramine Maleate, Brompheniramine Maleate, ChlorcyclizineHydrochloride, Thonzylamine Hydrochloride, Pyrilamine Maleate,Phenindamine Tartrate, or any approved oral antihistamine; Guaifenesinor any approved oral expectorant; Acetaminophen or any approvedanalgesic, antipyretic or anti-inflammatory; Citric Acid; SodiumCitrate; Propylene Glycol; Flavor; Sodium Saccharin Solution (SodiumSaccharin dissolved in water or any other solvent); Sorbitol; Glycerin;and Purified Water

The formulations of the invention may be combined with any of thefollowing pharmaceutical aids or excipients or preservatives, added assolutions, suspension, emulsions, or directly added as liquids orpowders: Preservatives—including but not limited to the following:Parabens, Benzoates, Sorbates; Artificial Sweeteners—including but notlimited to the following: Sucralose, Saccharin, Acesulfame;Sweeteners—including but not limited to the following: Sucrose, CornSyrup, High Fructose Corn Syrup, Maltitol, Mannitol, Dextrose, Glucose;Thickeners—including but not limited to the following: Gums, Mucilages,Xanthan Gum, Guar Gum, Veegum, Methylcellulose Derivatives; BufferingAgents—including but not limited to the following: Phosphates, Citrates,Sulfates, Carbonates, etc.; Alcohol and Alcohol Derivatives as Solvents,Preservatives, Flavors; Emulsifiers; Coloring Agents, Dyes, CertifiedColors; Any and all pharmaceutical excipients

While the present invention has been illustrated by the description ofembodiments thereof, and while the embodiments have been described inconsiderable detail, it is not intended to restrict or in any way limitthe scope of the appended claims to such detail. Additional advantagesand modifications will be readily apparent to those skilled in the art.The invention in its broader aspects is, therefore, not limited to thespecific details, representative method, and illustrated examplesdescribed. Accordingly, departures may be made from such details withoutdeparting from the scope or spirit of Applicant's general inventiveconcept.

Examples of the compositions of the invention are set forth below:

ACTIVE 1 ACTIVE 2 ACTIVE 3 Chlophedianol HCl 12.5 mg Pseudoephedrine HCl30 mg Dexchlorpheniramine Maleate 1 mg Chlophedianol HCl 12.5 mgPseudoephedrine HCl 30 mg Guaifenesin 100 mg Chlophedianol HCl 12.5 mgPseudoephedrine HCl 30 mg Guaifenesin 200 mg Chlophedianol HCl 12.5 mgPseudoephedrine HCl 30 mg Chlorcyclizine 9.375 mg Chlorcyclizine HCl9.375 mg Pseudoephedrine HCl 30 mg Chlophendianol HCl 25 mg Guaifenesin200 mg Chlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mgChlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mg Codeine Phosphate10 mg Chlorcyclizine HCl 9.375 mg Codeine Phosphate 10 mg ChlophedianolHCl 12.5 mg Dexbrompheniramine 1 mg Phenylephrine HCl 5 mg ChlophedianolHCl 25 mg Pseudoephedrine HCl 60 mg Chlorpheniramine Maleate 4 mgChlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mg Chlophedianol HCl12.5 mg Chlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mgDextromethorphan HBr 15 mg Chlophedianol HCl 12.5 mg Guaifenesin 100 mgPhenylephrine HCl 5 mg Thonzylamine HCl 50 mg Codeine Phosphate 10 mgThonzylamine HCl 50 mg Codeine Phosphate 10 mg Pseudoephedrine HCl 30 mgChlophedianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Chlophedianol HCl12.5 mg Dexbrompheniramine 1 mg Phenylephrine HCl 5 mg Chlophedianol HCl12.5 mg Pseudoephedrine HCl 30 mg Brompheniramine Maleate 2 mgChlophedianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Chlorcyclizine 9.375mg Chlophedianol HCl 25 mg Pseudoephedrine HCl 60 mg Chlorcyclizine18.75 mg Chlophedianol HCl 12.5 mg Phenylephrine HCl 5 mg Chlorcyclizine9.375 mg Chlophedianol HCl 25 mg Phenylephrine HCl 10 mg Chlorcyclizine18.75 mg Chlophendianol HCl 25 mg Pseudoephedrine HCl 60 mg Pyrilaminemaleate 50 mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mgGuaifenesin 200 mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mgGuaifenesin 400 mg Chlophendianol HCl 12.5 mg Guaifenesin 100 mgChlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Thonzylamine HCl 50mg Chlophendianol HCl 25 mg Pseudoephedrine HCl 60 mg Thonzylamine HCl100 mg Chlophendianol HCl Phenylephrine HCl 5 Thonzylamine HCl 50 mg12.5 mg mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mg ThonzylamineHCl 100 mg Chlophendianol HCl 25 mg Guaifenesin 400 mg ChlophendianolHCl 25 mg Pseudoephedrine HCl 60 mg Guaifenesin 400 mg ChlorcyclizineHCl 9.375 Phenylephrine HCl 5 mg Chlorcyclizine HCl 18.75 mgPhenylephrine HCl 10 mg Chlorcyclizine HCl 18.75 mg Pseudoephedrine HCl60 mg Thonzylemine HCl 50 mg Pseudoephedrine HCl 30 mg Thonzylemine HCl100 mg Pseudoephedrine HCl 60 mg Thonzylemine HCl 50 mg PhenylephrineHCl 5 mg Thonzylemine HCl 100 mg Phenylephrine HCl 10 mg ChlorcyclizineHCl 9.375 mg Pseudoephedrine HCl 30 mg Acetaminophen 325 mg ThonzylamineHCl 50 mg Pseudoephedrine HCl 30 mg Acetaminophen 325 mg ChlorcyclizineHCl 18.75 mg Pseudoephedrine HCl 60 mg Acetaminophen 500 mg ThonzylamineHCl 100 mg Pseudoephedrine HCl 60 mg Acetaminophen 500 mg ChlophendianolHCl 12.5 mg Pseudoephedrine HCl 30 mg Thonzylamine HCl 50 mgChlophendianol HCl 25 mg Pseudoephedrine HCl 60 mg Thonzylamine HCl 100mg Chlophendianol HCl Phenylephrine HCl 5 mg Thonzylamine HCl 50 mg 12.5mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mg Thonzylamine HCl 100mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Chlorcyclizine HCl9.375 mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mg ChlorcyclizineHCl 18.75 mg Chlophendianol HCl 25 mg Pseudoephedrine HCl 60 mgGuaifenesin 200 mg Chlophendianol HCl 25 mg Phenylephrine HCl 10 mgBrompheniramine 4 mg Chlorcyclizine HCl 9.375 mg Codeine Phosphate 10 mgPseudoephedrine HCl 30 mg Chlorcyclizine HCl 9.375 mg Codeine Phosphate10 mg Acetaminophen 325 mg Thonzylamine HCl 50 mg Codeine Phosphate 10mg Pseudoephedrine HCl 30 mg Thonzylamine HCl 50 mg Codeine Phosphate 10mg Acetaminophen 325 mg Thonzylamine HCl 50 mg Codeine Phosphate 10 mgPhenylephrine HCl 5 mg Chlorcyclizine HCl 9.375 mg Codeine Phosphate 10mg Phenylephrine HCl 5 mg Chlorcyclizine HCl 9.375 mg Codeine Phosphate10 mg Phenylephrine HCl 5 mg Thonzylamine HCl 50 mg Codeine Phosphate 10mg Phenylephrine HCl 5 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl30 mg Chlorpheniramine Maleate 2 mg Chlophendianol HCl 12.5 mgPseudoephedrine HCl 30 mg Dexbrompheniramine Maleate 1 mg ThonzylamineHCl 50 mg Pseudoephedrine HCl 30 mg Dextromethorphan HBr 15 mgThonzylamine HCl 50 mg Phenylephrine HCl 5 mg Dextromethorphan HBr 15 mgChlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mg DextromethorphanHBr 15 mg Chlorcyclizine HCl 9.375 mg Phenylephrine HCl 5 mgDextromethorphan HBr 15 mg Chlophedinol HCl 12.5 mg Pseudoephedrine HClGuaifenesin 75 mg 30 mg Chlorcyclizine HCl 9.375 mg Pseudoephedrine HCl30 mg Dextromethorphan HBr 15 mg Thonzylamine HCl 50 mg PhenylephrineHCl 5 mg Dextromethorphan HBr 15 mg Chlophendianol HCl 12.5 mgPhenylephrine HCl 5 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mgPseudoephedrine HCl 30 mg Pyrilamine Maleate 25 mg Chlophendianol HCl12.5 mg Phenylephrine HCl 5 mg Pyrilamine Maleate 25 mg ChlophendianolHCl Pseudoephedrine HCl 30 mg Guaifenesin 100 mg 12.5 mg ChlophendianolHCl 25 mg Pseudoephedrine HCl 60 mg Guaifenesin 200 mg ChlophendianolHCl 12.5 mg Phenylephrine HCl 5 mg Guaifenesin 100 mg Chlophendianol HCl25 mg Phenylephrine HCl 10 mg Guaifenesin 200 mg Chlophendianol HCl 25mg Pseudoephedrine HCl 60 mg Guaifenesin 400 mg Chlophendianol HCl 25 mgPhenylephrine HCl 10 mg Guaifenesin 400 mg Chlophendianol HCl 12.5 mgPseudoephedrine HCl 30 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mgPhenylephrine HCl 5 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mgPseudoephedrine HCl 30 mg Doxylamine Succinate 6.25 mg ChlophendianolHCl 12.5 mg Pseudoephedrine HCl 30 mg Doxylamine Succinate 6.25 mgChlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Doxylamine Succinate6.25 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg DoxylamineSuccinate 6.25 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mgDiphenhydramine HCl 25 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5mg Diphenhydramine HCl 25 mg Chlophendianol HCl 12.5 mg PseudoephedrineHCl 30 mg Diphenhydramine HCl 25 mg Chlophendianol HCl 12.5 mgPhenylephrine HCl 5 mg Diphenhydramine HCl 25 mg Chlophendianol HCl 12.5mg Guaifenesin 200 mg Chlophendianol HCl 8.33 mg Brompheniramine 1.33 mgPhenylephrine 33.33 mg Chlorcyclizine HCl 25 mg Pseudoephedrine HCl 60mg Codeine Phosphate 10 mg Thonzylamine HCl 100 mg Pseudoephedrine HCl60 mg Codeine Phosphate 10 mg Chlorcyclizine HCl 25 mg PseudoephedrineHCl 60 mg Chlorcyclizine HCl 25 mg Chlophedianol HCl 25 mgChlorcyclizine HCl 25 mg Chlophedinol HCl 25 mg Pseudoephedrine HCl 60mg Chlorcyclizine HCl 25 mg Chlophedianol HCl 12.5 mg Chlophedianol HCl25 mg Thonzylamine HCl 100 mg Codeine Phosphate 10 mg Thonzylamine HCl100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 30 mg ThonzylamineHCl 100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 15 mgThonzylamine HCl 100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr20 mg Chlorcyclizine HCl 25 mg Pseudoephedrine HCl 60 mgDextromethorphan HBr 30 mg Dextromethorphan HBr 15 mg Chlorcyclizine HCl9.373 Dextromethorphan HBr 30 mg Chlorcyclizine HCl HBr 18.75 mgDextromethorphan HBr 15 mg Thonzylamine HCl 50 mg Dextromethorphan HBr30 mg Thonzylamine HCl 100 mg Chlophedianol HCl 12.5 mg Thonzylamine HCl50 mg Chlophedianol HCl 12.5 mg Chlorcyclizine HCl 9.375 mg

What is claimed is:
 1. A pharmaceutical composition for alleviatingsymptoms of upper respiratory and oral-pharyngeal congestion in asubject, the composition comprising: a first active ingredientcomprising at least one of chlophedianol hydrochloride, chlorcyclizinehydrochloride, phenylephrine hydrochloride, dextromethorphanhydrobromide and thonzylamine hydrochloride, morphine, diacetylmorphine,oxymorphone, hydromorphone, dextromethorphan, levorphanol, oxycodone,nalmefene, methadone, meperidine, pentazocine, buprenorphine,nalbuphine, butorphanol, sufentanyl, alfentanyl, propoxyphene,nalorphine, naloxone, naltrexone and fentanyl; a second activeingredient selected from the group consisting of hydroxyzine,chloropheniramine, acepromazine, aceprometazine, alimemazine,alimemazine tartrate, amoxydramine camsilate, antazoline chlorhydrate,antazoline mesilate, antazoline phosphate, bamipine hydrochloride,benactyzine hydrochloride, bretylium tosilate, bromazine hydrochloride,buclizine dihydrochloride, bufexamac, chlorphenamine maleate,chlorphenoxamine hydrochloride, chlorprothixene hydrochloride,cinnarizine, clemastine fumarate, clemizole hexachlorophenate, clemizolepenicilline, clemizole undecylenate, clocinizine dihydrochloride,clofedanol, clofenetamine hydrochloride, difencloxazine, dimelazinehydrochloride, dimenhydrinate, dimethoxanate hydrochloride,cimetotiazine mesilate, diphenylpyraline hydrochloride, diproqualonecamsilate, dixyrazine, eprozinol dihydrochloride, etodroxizinedimaleate, etybenzatropine bromhydrate, etybenzatropine hydrochloride,etymemazine hydrochloride, fenethazine hydrochloride, fenoxazolinehydrochloride, fenpentadiol, flunarizine hydrochloride, flupentixoldecanoate, flupentixol dihydrochloride, histapyrrodine hydrochloride,hydroxyzine dihydrochloride, hydroxyzine embonate, indoraminehydrochloride, isothipendyl hydrochloride, levomepromazine,levomepromazine hydrochloride, levomepromazine embonate, levomepromazinemaleate, maprotiline hydrochloride, maprotiline mesilate, maprotilineresinate, meclozine hydrochloride, mecysteine hydrochloride,medifoxamine fumarate, mefenidramium metilsulfate, mepyramine maleate,mequitazine, methaqualone, methdilazine hydrochloride, metixenehydrochloride, moxisylyte hydrochloride, niaprazine, orphenadrinehydrochloride, oxaflumazine disuccinate, oxatomide, oxolamine benzilate,oxolamine citrate, oxomemazine, oxomemazine hydrochloride, parathiazineteoclate, perimetazine, phenoxybenzamine hydrochloride,phenyltoloxamine, phenyltoloxamine citrate, pimethixene, pipotiazine,pipretecol dihydrochloride, pizotifene malate, prednazoline, profenaminehydrochloride, promethazine, promethazine hydrochloride, promethazineembonate, promethazine polyvinylbenzene-metacrylate, propiomazine,thenalidine tartrate, thenyldiamine hydrochloride, and thiazinamiummetilsulfate.
 2. The pharmaceutical composition of claim 1, furthercomprising a third active ingredient selected from the group consistingof phenylethylamine, epinephrine, norepinephrine, dopamine, dobutamine,colterol, ethylnorepinephrine, isoproterenol, isoetharine,metaproterenol, terbutaline, metaraminol, phenylephrine, tyraine,hydroxy amphetamine, ritodrine, prenalterol, methoxyamine, albuterol,amphetamine, methamphetamine, benzphetamine, ephedrine,phenylpropanolamine, mephentermine, phentermine, fenfluramine,propylhexedrine, diethylpropion, phenmetrazine, phendimetrazine,oxymetazoline, and xylometazoline.
 3. The pharmaceutical composition ofclaim 1, wherein the first active ingredient is present at a range of9.375 mg to 100 mg.
 4. The pharmaceutical composition of claim 1,wherein the second active ingredient is present at a range of 1 mg to100 mg.
 5. The pharmaceutical composition of claim 2, wherein thirdactive ingredient is present at a range of 1 mg to 500 mg.